Prostate-sparing effects in primates of the potent androgen 7alpha-methyl-19-nortestosterone: a potential alternative to testosterone for androgen replacement and male contraception

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Abstract

7alpha-Methyl-19-nortestosterone (MENT) is a potent synthetic androgen
that cannot be converted to dihydrotestosterone. In this study we
determined the relative androgenic, antigonadotropic, and anabolic
potencies of testosterone vs. MENT in the nonhuman primate M.
fascicularis. In castrated monkeys, dose-response relationships were
generated for the effects of testosterone and MENT on gonadotropin levels,
prostate growth, body weight, and lipid metabolism. In a pilot study, four
monkeys were castrated, and magnetic resonance imaging (MRI) was used to
document a 50% loss of prostate volume within 8 weeks, verifying that MRI
is a reliable means to measure prostate size in this species. Two
additional groups of six monkeys each were then castrated and serially
administered four graded dosages of testosterone or MENT via osmotic
minipumps over 20 weeks. Complete suppression of LH was achieved with a
minimum of 0.3 mg/day MENT, compared to 3.0 mg/day testosterone. MENT
supported body weight 10 times more potently than did testosterone.
Baseline prostate volumes were maintained with 0.1-0.2 mg/day MENT vs. 0.3
mg/day testosterone. Thus, in monkeys, MENT is 10 times more potent than
testosterone with regard to the clinically desirable end points of
gonadotropin suppression and anabolism, but only twice as potent at
stimulating prostate growth. These results suggest that MENT may have a
wider therapeutic index than testosterone for human androgen replacement
and male contraception.